A multicenter, randomized, open label, two formulation, crossover bioequivalence trial of doxorubicin hydrochloride liposomal injection in Chinese patients with metastatic breast cancer.

Purpose: The primary objectives of this trial were aimed at exploring the pharmacokinetic profiles and the human bioequivalence of an intravenous liposomal injection of doxorubicin hydrochloride in comparison with a reference formulation in Chinese patients diagnosed with metastatic breast cancer.

Methods: To achieve these goals, the trial employed a randomized, open-label, two-formulation crossover dosing strategy among Chinese patients with metastatic breast cancer. Pharmacokinetic (PK) evaluation was conducted through the collection of blood samples, and the liquid chromatography tandem mass spectrometry (LC/MS/MS) method was leveraged to quantify plasma concentrations of both liposome-encapsulated doxorubicin and non-encapsulated doxorubicin in patients.

A novel therapeutic strategy utilizing EpCAM aptamer-conjugated gemcitabine for targeting bladder cancer and cancer stem cells.

Gemcitabine (GEM) is a first line chemotherapy drug for bladder cancer (BCa). GEM's lack of specificity has led to disadvantages, resulting in low efficiency, especially when combined with the targeted treatment of BCa stem cells (CSCs), which is considered the cause of BCa recurrence and progression. To enhance the anti-cancer effect and reduce the side effects of GEM targeting of BCa cells/CSCs, an aptamer drug conjugate (ApDC) targeted delivery system was used to improve the efficiency of GEM in BCa therapy using EpCAM aptamer-GEM conjugates based on the epithelial cell adhesion molecule (EpCAM), which is highly expressed on the cell membrane of BCa cells/CSCs.

Deep Learning-Enabled Integration of Histology and Transcriptomics for Tissue Spatial Profile Analysis.

Spatially resolved transcriptomics enable comprehensive measurement of gene expression at subcellular resolution while preserving the spatial context of the tissue microenvironment. While deep learning has shown promise in analyzing SCST datasets, most efforts have focused on sequence data and spatial localization, with limited emphasis on leveraging rich histopathological insights from staining images. We introduce GIST, a deep learning-enabled gene expression and histology integration for spatial cellular profiling.

Basic helix-loop-helix ARNT like 1 regulates the function of immune cells and participates in the development of immune-related diseases.

The circadian clock is an internal timekeeper system that regulates biological processes through a central circadian clock and peripheral clocks controlling various genes. Basic helix-loop-helix ARNT-like 1 (), also known as aryl hydrocarbon receptor nuclear translocator-like protein 1 (), is a key component of the circadian clock. The deletion of alone can abolish the circadian rhythms of the human body.

IBI310 plus sintilimab vs. placebo plus sintilimab in recurrent/metastatic cervical cancer: A double-blind, randomized controlled trial.

Background: It remains unclear whether adding CTLA-4 blockade to PD-1/PD-L1 blockade improves clinical outcomes in cervical cancer (CC).

Methods: In this randomized, double-blind, placebo-controlled, phase 2 study (ClinicalTrials.gov: NCT04590599), patients with recurrent/metastatic CC (R/M CC) who experienced disease progression after or during platinum-based chemotherapy were enrolled from 37 centers across China and randomly assigned (1:1), stratified by PD-L1 expression and prior treatment lines, to receive either IBI310 plus sintilimab or placebo plus sintilimab intravenously every 3 weeks for 12 weeks, followed by sintilimab alone.

Protein kinase A suppresses anti-proliferative effect of interferon-α in hepatocellular carcinoma by activation of protein tyrosine phosphatase SHP2.

Src homology-2-containing protein tyrosine phosphatase 2 (SHP2) plays a dual role in cancer initiation and progression. Identifying signals that modulate the function of SHP2 can improve current therapeutic approaches for IFN-α/β in HCC. We showed that cAMP-dependent protein kinase A (PKA) suppresses IFN-α/β-induced JAK/STAT signaling by increasing the phosphatase activity of SHP2, promoting the dissociation of SHP2 from the receptor for activated C-kinase 1 (RACK1) and binding to STAT1.

Engineering a wirelessly self-powered neural scaffold based on primary battery principle to accelerate nerve cell differentiation.

Electrical stimulation displayed tremendous potential in promoting nerve regeneration. However, the current electrical stimulation therapy required complex traversing wires and external power sources, which significantly limited its practical application. Herein, a self-powered nerve scaffold based on primary battery principle was gradient printed by laser additive manufacturing technique.

Exploring treatment-driven subclonal evolution of prognostic triple biomarkers: Dual gene fusions and chimeric RNA variants in novel subtypes of acute myeloid leukemia patients with KMT2A rearrangement.

Chromosomal rearrangements (CR) initiate leukemogenesis in approximately 50 % of acute myeloid leukemia (AML) patients; however, limited targeted therapies exist due to a lack of accurate molecular and genetic biomarkers of refractory mechanisms during treatment. Here, we investigated the pathological landscape of treatment resistance and relapse in 16 CR-AML patients by monitoring cytogenetic, RNAseq, and genome-wide changes among newly diagnosed, refractory, and relapsed AML. First, in FISH-diagnosed KMT2A (MLL gene, 11q23)/AFDN (AF6, 6q27)-rearrangement, RNA-sequencing identified an unknown CCDC32 (15q15.

Protective role of triiodothyronine in sepsis‑induced cardiomyopathy through phospholamban downregulation.

Sepsis is often a cause of mortality in patients admitted to the intensive care unit. Notably, the heart is the organ most susceptible to the impact of sepsis and this condition is referred to as sepsis‑induced cardiomyopathy (SIC). Low triiodothyronine (T3) syndrome frequently occurs in patients with sepsis, and the heart is one of the most important target organs for the action of T3.

Lerociclib plus fulvestrant in patients with HR+/HER2- locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: LEONARDA-1 a phase III randomized trial.

Lerociclib (GB491), a highly selective oral CDK4/6 inhibitor, has displayed anti-tumor activity and differentiated safety and tolerability profile in previous ph1/2 clinical trials. The LEONARDA-1, a randomized, double-blind, phase III study, was conducted to evaluate the efficacy and safety of lerociclib in HR+/HER2- locally advanced or metastatic breast cancer patients, who had relapsed or progressed on prior endocrine therapy. A total of 275 patients were randomized at 1:1 ratio to receive lerociclib (137 patients, 150 mg twice daily) or placebo (138 patients) plus fulvestrant.

Hepatic adverse events associated with ketamine and esketamine: A population-based disproportionality analysis.

Background And Objective: To determine whether there is disproportionate reporting of hepatobiliary disorders in the United States (US) FDA Adverse Event Reporting System (FAERS) for individuals prescribed ketamine or esketamine.

Design: We identified Medical Dictionary for Regulatory Activities (MedDRA) terms in the FAERS related to hepatobiliary disorders.

Main Measures: Formulations of ketamine and esketamine were evaluated for the proportionality of reporting for each hepatobiliary disorder parameter using the reporting odds ratio (ROR).

Acute inflammation induces acute megakaryopoiesis with impaired platelet production during fetal hematopoiesis.

Hematopoietic development is tightly regulated by various factors. The role of RNA m6A modification during fetal hematopoiesis, particularly in megakaryopoiesis, remains unclear. Here, we demonstrate that loss of m6A methyltransferase METTL3 induces formation of double-stranded RNAs (dsRNAs) and activates acute inflammation during fetal hematopoiesis.

Correlation between cathepsins and the likelihood of renal cancer: a Mendelian randomization study.

Background: Previous studies have established a relationship between cathepsins and renal cancer. Nonetheless, the specific causal connection between the two factors continues to be ambiguous. The aim of this study is to evaluate the causal relationship between cathepsins and renal cancer via employing Mendelian randomization (MR).

Elucidating stearoyl metabolism and NCOA4-mediated ferroptosis in gastric cancer liver metastasis through multi-omics single-cell integrative mendelian analysis: advancing personalized immunotherapy strategies.

Background: The metabolism of stearoyl-GPE plays a key role in the liver metastasis of gastric cancer. This investigation delves into the mechanisms underlying the intricate tumor microenvironment (TME) heterogeneity triggered by stearoyl metabolism in gastric cancer with liver metastasis (LMGC), offering novel perspectives for LMGC.

Objective: Utilizing Mendelian randomization, we determined that stearoyl metabolism significantly contributes to the progression of gastric cancer (GC).

Deep learning of noncontrast CT for fast prediction of hemorrhagic transformation of acute ischemic stroke: a multicenter study.

Background: Hemorrhagic transformation (HT) is a complication of reperfusion therapy following acute ischemic stroke (AIS). We aimed to develop and validate a model for predicting HT and its subtypes with poor prognosis-parenchymal hemorrhage (PH), including PH-1 (hematoma within infarcted tissue, occupying < 30%) and PH-2 (hematoma occupying ≥ 30% of the infarcted tissue)-in AIS patients following intravenous thrombolysis (IVT) based on noncontrast computed tomography (NCCT) and clinical data.

Methods: In this six-center retrospective study, clinical and imaging data from 445 consecutive IVT-treated AIS patients were collected (01/2018-06/2023).

Association of whole grain food consumption with lung cancer risk: a prospective cohort study.

Background: Whether the intake of whole grain foods can protect against lung cancer is a long-standing question of considerable public health import, but the epidemiologic evidence has been limited. Therefore we aim to investigate the relationship between whole grain food consumption and lung cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort.

Methods: Diet was assessed with a self-administered Diet History Questionnaire (DHQ) at baseline.

Dynamic switching between brain networks predicts creative ability.

Creativity is hypothesized to arise from a mental state which balances spontaneous thought and cognitive control, corresponding to functional connectivity between the brain's Default Mode (DMN) and Executive Control (ECN) Networks. Here, we conduct a large-scale, multi-center examination of this hypothesis. Employing a meta-analytic network neuroscience approach, we analyze resting-state fMRI and creative task performance across 10 independent samples from Austria, Canada, China, Japan, and the United States (N = 2433)-constituting the largest and most ethnically diverse creativity neuroscience study to date.

Gut microbial GABA imbalance emerges as a metabolic signature in mild autism spectrum disorder linked to overrepresented Escherichia.

Gut microbiota (GM) alterations have been implicated in autism spectrum disorder (ASD), yet the specific functional architecture remains elusive. Here, employing multi-omics approaches, we investigate stool samples from two distinct cohorts comprising 203 children with mild ASD or typical development. In our screening cohort, regression-based analysis for metabolomic profiling identifies an elevated γ-aminobutyric acid (GABA) to glutamate (Glu) ratio as a metabolic signature of ASD, independent of age and gender.

Transcatheter rectal arterial chemoembolization with oxaliplatin and concurrent chemoradiotherapy in patients with locally advanced rectal cancer: A retrospective comparative study.

Background: The aim of the study is to assess whether transcatheter rectal arterial chemoembolization (TRACE) with oxaliplatin could increase the pathologic complete response (pCR) rate of locally advanced rectal cancer (LARC) and improve survival outcomes, while minimizing adverse events compared to preoperative chemoradiotherapy (CRT) alone.

Methods: Eligible LARC patients who received TRACE with oxaliplatin plus chemoradiotherapy (the NATRACE-CRT group) or preoperative CRT alone (the NA-CRT group) were retrospectively selected from the database of our institution. Pathological results, treatment-related adverse events and survival in the two groups were compared.

Advancing allergic rhinitis research through phenome-wide association studies: Insights from known genetic loci.

Background: Allergic rhinitis (AR) is a common chronic respiratory disease that can lead to the development of various other conditions. Although genetic risk loci associated with AR have been reported, the connections between these loci and AR comorbidities or other diseases remain unclear.

Methods: This study conducted a phenome-wide association study (PheWAS) using known AR risk loci to explore the impact of known AR risk variants on a broad spectrum of phenotypes.

The microenvironment cell index is a novel indicator for the prognosis and therapeutic regimen selection of cancers.

Background: It is worthwhile to establish a prognostic prediction model based on microenvironment cells (MCs) infiltration and explore new treatment strategies for triple-negative breast cancer (TNBC).

Methods: The xCell algorithm was used to quantify the cellular components of the TNBC microenvironment based on bulk RNA sequencing (bulk RNA-seq) data. The MCs index (MCI) was constructed using the least absolute shrinkage and selection operator Cox (LASSO-Cox) regression analysis.

Fruquintinib Plus Sintilimab in Patients with Treatment-Naive and Previously Treated Advanced Renal Cell Carcinoma: Results from a Phase Ib/II Clinical Trial.

Background: Antiangiogenic inhibitors plus immune checkpoint inhibitors have synergistic antitumor activity and have improved treatment outcomes in patients with renal cell carcinoma (RCC).

Objective: We report the RCC cohort from a phase Ib/II study in Chinese patients evaluating the efficacy and safety of fruquintinib plus sintilimab in treating advanced clear cell RCC (ccRCC).

Patients And Methods: Eligible patients had pathologically confirmed advanced ccRCC.

Ultrasound-triggered drug-loaded nanobubbles for enhanced T cell recruitment in cancer chemoimmunotherapy.

Chemotherapy combined with immunotherapy is a highly promising approach for treating tumors. However, chemotherapeutic drugs often fail to accumulate effectively at the tumor site after systemic administration and they lack sufficient immunogenicity to activate adaptive immunity, making an effective T-cell immune response within the tumor microenvironment difficult to achieve. Here, this work developed drug-loaded nanobubbles (DTX-R837@NBs) that encapsulate the chemotherapy drug docetaxel and the immune adjuvant R837 via a thin-film hydration method.

Chromatin landscape alteration uncovers multiple transcriptional circuits during memory CD8+ T cell differentiation.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells.